In recent years, coronary cardio-circulary diseases, e.g., atherosclerosis and hypercholesterolemia, have increasingly become a major cause of deaths. It has been reported that an elevated plasma cholesterol level causes the deposition of fat, macrophages and foam cells on the wall of blood vessels, such deposit leading to plaque formation and then to atherosclerosis (Ross, R., Nature, 362, 801-809(1993)). One of the methods for decreasing the plasma cholesterol level is alimentotherapy to reduce the ingestion of cholesterol and lipids. Another method is to lower the rate of cholesterol biosynthesis which takes place in the liver. It has been reported that hypercholesterolemia can be treated effectively by reducing the rate of cholesterol biosynthesis through the inhibition of HMG--CoA reductase which mediates the synthesis of mevalonic acid, an intermediate in the biosynthesis of sterols or isoprenoids (Cardiovascular Pharmacology, William W. Parmley and Kanu Chatterjee Ed., Wolfe Publishing, pages 8.6-8.7, 1994).
Therefore, numerous efforts have been made to develop medicines to inhibit HMG--CoA reductase; and, as a result, several compounds derived from Penicillium sp. and Aspergillus sp. have been commercialized. Specifically, Lovastatin.RTM. and Simvastatin.RTM. developed by Merck Co., U.S.A., and Pravastatin.RTM. developed by Sankyo Co., Japan, have been commercialized (C. D. R. Dunn, Stroke: Trends, Treatment and Markets, SCRIPT Report, PJB Publications Ltd., 1995). However, these medicines are very expensive and a long-term administration thereof is known to induce an adverse side effect of increasing creatine kinase in the liver. Accordingly, there has continued to exist a need to develop an inexpensive and non-toxic inhibitor of HMG--CoA reductase.
Naringin and the aglycon of naringin, naringenin, are flavonoids found in lemons, grapefruits, tangerines and oranges (Citrus sinensis) and they have the following structures (Horowitz, Gentili, Tetrahedron, 19, 773(1963)): ##STR1##
Naringin has been used as a bitter tasting agent, sweetner or chewing gum base. However, there has been no report on the HMG--CoA reductase inhibitory activity of naringin or naringenin.